Stem cells refer to cells having not only self-replicating ability but also the ability to differentiate into at least two types of cells, and can be divided into totipotent stem cells, pluripotent stem cells, and multipotent stem cells.
Totipotent stem cells are cells having totipotent properties capable of developing into one perfect individual, and these properties are possessed by cells up to the 8-cell stage after the fertilization of an oocyte and a sperm. When these cells are isolated and transplanted into the uterus, they can develop into one perfect individual. Pluripotent stem cells, which are cells capable of developing into various cells and tissues derived from the ectodermal, mesodermal and endodermal layers, are derived from an inner cell mass located inside of blastocysts generated 4-5 days after fertilization. These cells are called “embryonic stem cells” and can differentiate into various other tissue cells but not form new living organisms. Multipotent stem cells, which are stem cells capable of differentiating into only cells specific to tissues and organs containing these cells, are involved not only in the growth and development of various tissues and organs in the fetal, neonatal and adult periods but also in the maintenance of homeostasis of adult tissue and the function of inducing regeneration upon tissue damage. Tissue-specific multipotent cells are collectively called “adult stem cells”.
Adult stem cells are obtained by taking cells from various human organs and developing the cells into stem cells and are characterized in that they differentiate into only specific tissues. However, recently, experiments for differentiating adult stem cells into various tissues, including liver cells, were dramatically successful, which comes into spotlight.
Efforts have been made in the field of regenerative medicine for regenerating biological tissues and organs and recovering their functions that were lost due to illness or accident and the like by using cells. Methods which are frequently used in this field of regenerative medicine comprise the steps of: collecting stem cells, blood-derived mononuclear cells or marrow-derived mononuclear cells from a patient; inducing the proliferation and/or differentiation of the cells by tube culture; and introducing the selected undifferentiated (stem cells and/or progenitor cells) and/or differentiated cells into the patient's body by transplantation. Accordingly, existing classical methods for treating diseases by medication or surgery are expected to be replaced with cell/tissue replacement therapy which replaces a damage cell, tissue or organ with healthy one, and thus the utility of stem cells will further increase.
Thus, the various functions of stem cells are currently being studied. Particularly, various studies on the efficient isolation of stem cells, the maintenance and proliferation of stem cells in an undifferentiated state and the differentiation of stem cells into tissue cells are in progress. There have been a number of reports on the migration of marrow-derived stem cells induced by treatment with chemokines (Adriana Lopez Ponte et al., Stem Cells, 25:1737-1745, 2007; Marek Honczarenko et al., Stem Cells, 24:1031-1041, 2006; Sordi V et al., Blood, 106:419-427, 2005; Fiedler J et al., J Cell Biochem, 87:305-312, 2002; Forte G et al., Stem Cells, 24:23-33, 2006; Wright D E et al., Blood, 87:4100-4108, 1996; Son B R et al., Stem Cells, 24:1254-1264, 2006), but there has been no report on the migration of adipose stem cells.
Accordingly, the present inventors have found that adipose mesenchymal stem cells have the ability to migrate and that the migration of adipose mesenchymal stem cells by a specific chemokine or growth factor is remarkably induced when the stem cells are primed with various chemokines or growth factors. Based on this finding, the present inventors have found a method capable of enhancing the ability of adipose-derived mesenchymal stem cells to express the receptors for chemokines or growth factors, thereby completing the present invention.